Hyperactive Delirium Temporally Associated With Hydroxyzine in a Child With Succinic Semialdehyde Dehydrogenase Deficiency Presenting With Psychotic Symptoms: A Case Report.

Abstract

Background: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of gamma-aminobutyric acid (GABA) metabolism caused by biallelic variants in ALDH5A1. The phenotype includes developmental delay, intellectual disability, seizures, sleep disturbance, anxiety, and other neurobehavioral symptoms. Psychotic symptoms are increasingly recognized in SSADHD but remain uncommon and incompletely characterized in children. In medically and neurodevelopmentally vulnerable patients, acute psychiatric decompensation may also be complicated by delirium, especially when severe sleep-wake disruption, poor intake, constipation, metabolic stress, and potentially deliriogenic medications are present.

Case presentation: We describe a 12-year-old girl with intellectual disability, global developmental delay, abnormal prior neuroimaging, abnormal EEG findings, progressive weight loss, reduced oral intake, insomnia, and new-onset auditory and visual hallucinations. During hospitalization, she developed a fluctuating neurobehavioral syndrome marked by impaired attention, severe sleep-wake disruption, increased startle response, inconsolability, agitation, perceptual disturbances, and waxing and waning behavioral organization. These findings supported hyperactive delirium superimposed on psychotic symptoms rather than isolated psychosis. Hydroxyzine was ordered as 25 mg by mouth every 6 h as needed and was administered six times from hospital day 5 through early hospital day 7. The medication provided mixed short-term anxiolytic and sedating benefits but did not meaningfully reduce hallucinations or restore normal sleep. After hydroxyzine exposure, impaired attention, profound sleep-wake dysregulation, inconsolability, increased startle response, fluctuating agitation, and behavioral disorganization remained prominent, raising concern that hydroxyzine may have contributed to persistence or worsening of the acute confusional state in the setting of severe sleep deprivation, poor oral intake, constipation, neurologic vulnerability, and underlying SSADHD. Hydroxyzine was discontinued, and low-dose quetiapine was initiated together with environmental sleep-wake and reorientation interventions. Sleep, appetite, oral intake, and behavioral regulation subsequently improved. Diagnostic evaluation supported SSADHD, including elevated urinary 4-hydroxybutyric acid, characteristic MRI abnormalities of the globi pallidi and dentate nuclei, and a homozygous ALDH5A1 missense variant, NM_001080.3:c.434A >G (p.Glu145Gly), formally classified as a variant of uncertain significance but considered clinically concordant with the diagnosis.

Conclusion: This case highlights SSADHD as an important consideration in children presenting with acute psychotic symptoms and altered mental status. It also underscores the importance of distinguishing psychotic symptoms from superimposed delirium in developmentally vulnerable patients. Because hallucinations, insomnia, poor intake, and behavioral dysregulation preceded hydroxyzine exposure and several competing contributors were present, hydroxyzine should be framed as a possible exacerbating or prolonging factor rather than the definitive sole cause of delirium. The case is therefore best described as hyperactive delirium temporally associated with, and possibly exacerbated by, hydroxyzine exposure.